The proposed study will examine levels and predictors of medication adherence among HIV+ active drug users, and a comparison group of drug users in recovery, as well as evaluate the usefulness of a brief placebo trial as a screening tool to determine readiness to adhere to highly active antiretroviral therapy (HAART) regimens. While the advent of HAART has led to significant gains in HIV clinical management and suppression of HIV viral activity, the complex and strict regimens associated with such treatment has raised concerns about adherence, particularly in subgroups such as active drug users. Many active drug users are not on combination antiretroviral therapy, in part because practitioners are cautious about prescribing these medications to patients suspected to be at high risk for nonadherence and development of drug resistance but also because drug users are often skeptical about the benefits of drug treatment or recognize that they are not yet prepared to follow the complex regimens. Findings to date have been mixed concerning the relationship between drug abuse, either past or current, and adherence to HAART, and little is known about the cognitive and behavioral processes associated with adherence in the context of-drug use. In Phase 1 of the proposed 3-year study, we will identify cognitive, behavioral and psychosocial correlates of adherence to a placebo regimen that mimics HAART. Adherence will be measured primarily with microelectronic monitoring caps over a 2-week observation period, among both active and former drug users who are not on HAART but who have significant immunosuppression. Subjects will be followed for up to 2 years; for those who initiate HAART adherence will be measured over a second 2-week period, which will constitute Phase 2. The primary goal of the study is to determine characteristics which identify the segment of the drug using population who are ready to effectively adhere to HAART. Results from this study will identify targets for interventions aimed at improving adherence among drug users, assess whether a placebo regimen is an effective screening tool for patients being considered for HAART, and inform public policy regarding the prescription of HAART to HIV+ patients with current substance use disorders.